Autosomal recessive congenital ichthyosis (ARCI) is a genetically and phenotypically heterogenous group of disorders that includes lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE). The incidence of ARCI cases has been estimated at approximately 1 in 200,000 births. Infants affected by LI and NCIE are generally born with a shiny, waxy layer of skin (called a collodion membrane) that is typically shed within the first few weeks of life. For LI patients, the skin beneath the collodion membrane is red and scaly, and typically develops into the large, dark, plate-like scales covering the skin which are characteristic of the disease. For NCIE patients, the skin beneath the collodion membrane is red and covered with fine, white scales, and skin abnormalities (such as thickening of the skin on the palms and the soles of the feet) may persist into adulthood.
The management of ARCI is a life-long endeavor, which remains largely symptomatic. At present, disease treatment or management is generally supportive, and commonly focuses on reducing scaling and/or skin lubrication. A first-line therapy typically includes hydration and lubrication of the skin accomplished by creams and ointments containing low concentrations of salt, urea, or glycerol, which may increase water binding capacity of the stratum corneum. Topical or oral retinoid therapy may be recommended for those with severe skin involvement; however, these medications can be associated with undesired long-term adverse effects (including mucocutaneous disorders, musculoskeletal disorders, abnormal lipid profile and transaminase elevation, and teratogenicity), and are therefore generally prescribed with caution. Thus, there exists a clear need for novel treatment options for ARCI. The present disclosure addresses this and other needs.
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